1. Field of the Invention
The present invention generally relates to the field of nanomaterials. More particularly, the present invention relates to treatment of cancer with self-assembling peptides.
2. Background Art
Prostate cancer (PCa) is responsible for the largest number of cancer deaths, with the exception of lung cancer. In the early stage, where the tumor is still localized, the disease can be cured by surgery or radioprostatectomy. However, due to the slow growing nature of the tumor, many PCa patients have already developed metastatic disease upon diagnosis and will inevitably enter the hormone refractory stage after hormone ablation therapy. There is currently no cure for hormone refractory prostate cancer (HRPC) at present. The most effective treatment regime for HRPC patients, Docetaxel-based chemotherapy, can only improve the median survival time for 3 months (12) (14). Therefore, effective treatment strategies against metastatic HRPC are urgently needed.
The reason that current therapies for metastatic HRPC fail is not completely understood. However, the isolation of cancer cells with stem-like characteristics provides solid evidence that prostate cancer stem cells (CSCs) may exist within the tumor. As in other types of cancer, prostate CSCs may account for the treatment failure; increasing evidence shows that current therapies are only successful in targeting the more differentiated tumor cells, sparing the putative cancer stem/progenitor cells (11). Like normal stem cells, CSCs are thought to be quiescent compared to mature cancer cells (7) (13) (6). This property makes CSCs resistance to chemotherapeutic drugs, which mainly target the actively replicating cells. The expression of multiple drug resistant gene (MDR1) (1) and ABC transporter (15) also help to protect the CSCs from cytotoxic drugs. In addition, prostate CSCs do not express androgen receptor; thus, they do not respond to hormone ablation in the same way as mature tumor cells. Therefore, elimination of the bulk of frequently replicating tumor cells, as well as the rare subset of slow dividing stem-like cells that are responsible for tumor regeneration, may represent a better therapeutic strategy in the treatment of PCa.
Due to their ability to self-renew and differentiate, prostate CSCs are capable of regenerating the heterogeneous tumor population (including both androgen-dependent and independent cells) and it is believed that CSCs may be responsible for the metastatic growth of primary prostate tumors (9). CSCs isolated from PCa cell lines have been found to be more invasive than the non-CSCs; likewise, PCa cells that are more invasive were found to possess stem cell characteristics. These results suggest that prostate CSCs may be the origin of prostate tumor metastasis and may be an ideal target for inhibiting disease metastasis. By limiting replication of CSCs, the progression of metastasis can be slowed. If the cells could be prevented from migrating away from the treatment area, it would allow for additional local targeting.
Previously, we demonstrated that by manipulating the cell density and concentration of the self-assembling peptide (SAP) material, we were able to control the proliferation, elongation, differentiation and maturation of cells in vitro. This included the nano environment surrounding PC12 cells, Schwann cells and neural precursor cells, as well as implants in the brain and spinal cord with and without cells (3). Here we show that prostate CSCs can be placed into stasis for an extended period of time without causing them to differentiate.